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Nanobodies®
creating better medicines
November 2015
Corporate presentation
2
Forward looking statements
Certain statements, beliefs and opinions in this presentation are forward-looking, which reflect the
Company or, as appropriate, the Company directors’current expectations and projections about
future events. By their nature, forward-looking statements involve a number of risks, uncertainties
and assumptions that could cause actual results or events to differ materially from those expressed
or implied by the forward-looking statements. These risks, uncertainties and assumptions could
adversely affect the outcome and financial effects of the plans and events described herein. A
multitude of factors including, but not limited to, changes in demand, competition and technology,
can cause actual events, performance or results to differ significantly from any anticipated
development. Forward looking statements contained in this presentation regarding past trends or
activities should not be taken as a representation that such trends or activities will continue in the
future. As a result, the Company expressly disclaims any obligation or undertaking to release any
update or revisions to any forward-looking statements in this presentation as a result of any
change in expectations or any change in events, conditions, assumptions or circumstances on
which these forward-looking statements are based. Neither the Company nor its advisers or
representatives nor any of its parent or subsidiary undertakings or any such person’s officers or
employees guarantees that the assumptions underlying such forward-looking statements are free
from errors nor does either accept any responsibility for the future accuracy of the forward-looking
statements contained in this presentation or the actual occurrence of the forecasted developments.
You should not place undue reliance on forward-looking statements, which speak only as of the
date of this presentation.
2
3
Ablynx
Corporate snapshot
• Platform technology and late-stage clinical development company
• 350 employees in Ghent, Belgium
• >30 wholly-owned and partnered programmes
• 1 Phase III and 4 Phase II studies ongoing in-house
• First potential product approval in 2018
• AbbVie, Boehringer Ingelheim, Eddingpharm, Genzyme, Merck &Co., Inc.,
Merck KGaA, Novartis, Novo Nordisk and Taisho Pharmaceutical
• >€380M cash received; >€7Bn in potential milestones + royalties
• €262M in cash at 30 September 2015
• €100M of issued Convertible Bonds maturing in 2020
CORPORATE
PARTNERS
PRODUCTS
FINANCIALS
• Pioneer in next generation antibody-derived drugs – Nanobodies®
• >500 patent applications and granted patents TECHNOLOGY
4
Abingworth Management Limited and
Abingworth LLP (UK), 6%
Boehringer Ingelheim (DE),
4%
Aviva Investors (UK), 5%
Perceptive Advisors (US), 4%
Polar Capital Funds Plc (UK),
3%
Oppenheimer Funds, Inc. (OFI)
(US); 3% FMR LLC (US),
5%
Taube Hodson Stonex Partners LLP (UK), 4%
Other institutional and retail
investors, 66%
Ablynx
• Ordinary shares listed on Euronext Brussels (ABLX)
• Sponsored Level I ADRs on the US OTC market (ABYLY)
• 54.5M shares outstanding
• 2.9M outstanding warrants
Diversified shareholder base
Total shares outstanding by investor
US 35%
UK 27%
Benelux 30%
Scandinavia 2%
France 3%
Other 3%
% of institutional shareholders by geography
(representing 68% of total S/O)
Unique technology
6
Nanobodies
• Camelid heavy-chain only antibodies are stable and fully functional
• Nanobodies represent the next generation of antibody-derived biologics
Derived from heavy-chain only antibodies
Conventional
antibodies
Heavy chain only
antibodies
Ablynx’s Nanobody
• small and robust
• easily linked together
• sequence homology comparable
to humanised/human mAbs
• nano- to picomolar affinities
• challenging and intractable targets
• multiple administration routes
• manufacturing in microbial cells
CH2
CH3
CH1
CL
VL
VH 12-15kDa
CH2
CH3
VHH
VHH
7
Ablynx’s drug discovery engine
Rapid generation of high quality biologics
~12-18 months
Immunise llamas
with antigen
and/or
Use proprietary synthetic
Nanobody phage libraries
Wide range of highly
diverse Nanobodies
with 0.1-10nM affinities
Formatted
Nanobodies
Cloning and
production in
microbial
systems
8
Ablynx’s Nanobodies
Competitive advantages
Mix and match
Cell specificity
Immune cell
recruitment
Tissue-specific
targeting
Cell- /tissue-homing
Albumin-
binding
Nanobody Fc
Weeks/days/hours
Customised
half-life extension
Nanobodies
against ion
channels and
GPCRs
Nanobodies can
reach conserved
cryptic epitopes
Challenging and
intractable targets
Manufacturing
High-yield,
high-
concentration,
low-viscosity,
microbial
production
Inhalation
Oral-to-topical
Needle-free
Ocular
Alternative delivery routes
Nanobody-
drug
conjugates
Cell killing
Ag-1 Ag-1 Ag-2
Targeting different pathways at once
with a single Nanobody construct, e.g.
multiple checkpoint inhibitors
Broad product pipeline
10
Hybrid business model fuels the pipeline
>30 programmes in development
Inflammation/
Immunology
FU
LL
Y O
WN
ED
Therapeutic area Product name Target
Inflammation/
Immunology
Haematology
Oncology/
Immuno-oncology
Respiratory
Discovery
ALX-0061
Pre-clinical Phase I Phase II Phase III
IL-6R
caplacizumab vWF
ALX-0171
Neurology
Various
ALX-0141 RANKL
ALX-0761
Various
Various
Various
RSV
Various
Various
PA
RT
NE
RE
D
Bone disorders Greater China
IL-17F/IL-17A
Ocular
Oncology/
Immuno-oncology
ozoralizumab TNFα Greater China
Filing
CXCR2
Various
Other
Clinically validated targets
First-in-class
Japan
Other Various
VEGF/Ang2
Key value drivers
12
Immuno-oncology (I/O)
*BofA Merrill Lynch July 2015
Changing the cancer treatment paradigm
• Proven substantial survival impact
• Market expected to grow to >$43bn by 2020*
• I/O drugs expected to treat 60% of cancers*
Huge market potential
• Increasing number of targets
• Combination therapies are the next generation
Multiple targets
Nature Reviews - 2012
• Bind multiple targets (2, 3, 4 or 5) with one Nanobody molecule
• Potential to increase efficacy and avoid escape mechanisms
• Technology allows rapid exploration of combinations
• Manufacturing simplicity and cost-effectiveness
Multi-specific Nanobodies
13
Immuno-oncology therapies
Best results when used in combination A
nti
-tu
mo
ur
acti
vit
y
Time course (months)
Sustained
response
Source: Prof Dr Omid Hamid (MD), Chief, Translational Research and Immunotherapy – The Angeles Clinic & Research Institute (2014)
14
Multi-specific Nanobodies
• Merck & Co., Inc. is a leader in the field
– heavily investing in I/O R&D pipeline (~80% of total R&D budget*)
– anti-PD-1 drug, Keytruda®, approved for the treatment of advanced melanoma and metastatic
NSCLC
– sales of Keytruda estimated to reach $6Bn by 2020**
– >160 clinical studies for Keytruda® across more than 30 tumor types as a monotherapy and in
combination
• Collaboration with Merck & Co., Inc. signed Feb ’14 and expanded in July ‘15
– targeting multiple immune-checkpoint modulators
– up to 17 Nanobody programmes with a focus on multi-specific combinations
– €33M up-front with potentially up to €5.7Bn in future milestones plus royalties
– first in vivo pre-clinical milestone (€3.5M) achieved with a bi-specific Nanobody in Oct 2015
*Bryan Garnier Oct 2015 **Leerink August 2015
Major immuno-oncology collaboration with Merck & Co., Inc.
15
PARTNERED
Programme (target) Indication Key differentiating features Stage Partner
ALX-0061 (IL-6R)
RA, SLE
Best-in-class opportunity
Monovalent interaction; strong affinity
and preferential binding to soluble IL-6R
3 Phase II studies (RA;
SLE) on-going; RA results
expected in H2 2016
Product pipeline
Leading products in the clinic
15
PROPRIETARY
Programme (target) Indication Key differentiating features Stage
Caplacizumab (vWF)
Thrombotic
thrombocytopenic
purpura
First-in-class orphan drug
Novel mode of action
Inhibition of micro-clot formation
Phase III on-going and MAA
filing in H1 2017 in EU for
conditional approval
ALX-0171 (RSV)
Respiratory
syncytial virus
infection
First-in-class addressing high unmet need
Inhaled Nanobody delivered to infection site
Highly potent trivalent construct
First-in-infant Phase IIa study
on-going: results expected in H1
2016
16
Caplacizumab
Wholly-owned anti-vWF Nanobody
• First-in-class bivalent Nanobody with Orphan Drug
Status and patent protection up to 2035
• Developed for the treatment of acquired thrombotic
thrombocytopenic purpura (aTTP)
• Phase II (75 patients) successfully completed; Phase
III (92 patients) on-going with results expected by
end of 2017
• Planning to file for conditional approval in Europe
(H1 2017) and BLA submission in USA (2018)
• Ablynx to lead commercialisation in Europe and USA
• Peak sales potential of €300M-€400M1
1 US, EU, Japan, other markets (Brazil, Canada, Russia, Mexico, Australia)
17
Caplacizumab mode of action
Stops formation of micro-clots
Caplacizumab blocks the platelet –
ULvWF interaction
ULvWF and anti-vWF Nanobody
ULvWF
Ex vivo assay for platelet string formation
Fluorescence microscopy image of platelets adhering to UL-vWF in plasma of TTP patients
Without treatment, fluorescently labelled platelets adhere to
UL-vWF, observed as string-like structures
Caplacizumab inhibits the formation of platelet strings and potentially
the associated microvascular thrombi in many organs
Ultra-Large (UL)
vWF multimers Platelet string
formation in patients
with TTP
ADAMTS13 activity is
impaired
endothelium
Caplacizumab binds to A1
domain of vWF and thereby
inhibits platelet string formation
18
Acquired TTP (aTTP)
• aTTP is caused by impaired activity of ADAMTS13 (<10% than that in normal plasma1)
– extensive micro-clot formation in small blood vessels throughout the body
– subsequent tissue ischemia and damage to vital organs
• Ultra-rare indication with an incidence of ~11/million2
• High unmet medical need with no approved therapeutic drug currently available
– mortality high (10-20%)3 and ~ 36% of patients relapse2
– major morbidities, including brain, cardiac and renal damage
1 Scully et al, BJH 2012; 2 George et al, EJH 2008; 3 Allford et al, BJH 2003, Kremer Hovinga, Blood 2010; Benhamou, Haematologica 2012
Life-threatening ultra-rare acute blood clotting disorder
aTTP patient Emergency Room ICU/haematology unit
episode diagnosis treatment
Sudden onset in otherwise healthy
person (nausea, fever, coma,..)
Initial diagnosis based on
thrombocytopenia & haemolysis
Plasma exchange until recovery of
platelet count + immune suppressants
19
Caplacizumab proven clinical benefit
Strong clinical proof-of-concept in TITAN Phase II study
Primary endpoint:
time to confirmed normalisation of
platelet count
Secondary endpoints:
exacerbations; relapses; PE parameters;
mortality; major clinical events
RA
ND
OM
ISA
TIO
N
1:1
PE
PE
Caplacizumab N=36
75 subjects
Placebo N=39
30 days
30 days 30 days
30 days
Study design Study results
Time to platelet
normalisation Caplacizumab Placebo
Median days (95% CI)
No prior PE
3.0 (2.7, 3.9)
N = 34
4.9 (3.2, 6.6)
N = 35
Median days (95% CI)
One prior PE
2.4 (1.9, 3.0)
N = 2
4.3 (2.9, 5.7)
N = 4
Number of subjects Caplacizumab Placebo
Subjects with exacerbation
within 30 days after
stopping daily PE
3 (8%) 11 (28%)
Deaths 0 2
• Primary endpoint met (p=0.005)
• 40% reduction in time to platelet normalisation
= faster reversion of thrombocytopenia
• 71% fewer patients with exacerbations
= potential prevention of further organ damage
20
Caplacizumab Phase III study
Double-blind placebo controlled study (Q3 2015 to Q4 2017)
* iv bolus (10mg) followed by daily sc (10mg)
** incl. corticosteroids at start of daily PE until underlying disease activity resolved
Primary endpoint: time to confirmed normalisation of platelet count
Secondary endpoints: exacerbations/relapses; mortality rate; severe morbidity; organ damage biomarkers
(troponin, creatinine, LDH); PE parameters; days in ICU/hospital; AEs; PD; PK; immunogenicity
RA
ND
OM
ISA
TIO
N
1:1
Caplacizumab* N=46
30 days
30 days
FOLLOW-UP PERIOD (4 weeks)
Potential extension of blinded study drug if relapse, restart daily PE and open label caplacizumab
Daily PE
Exacerbation restart daily PE and open label caplacizumab
Placebo* N=46
TREATMENT PERIOD**
Daily PE
92 subjects
21
Caplacizumab positioning
New standard of care in aTTP
21
Tre
ate
men
t du
ratio
n
Daily PE Immuno-
suppression
Remove ULvWF
& auto-antibodies
Replenish
ADAMTS13
Reduce activity
of immune
system to
resolve
underlying
cause of aTTP
Caplacizumab
Immediate inhibition of platelet
aggregation, micro clot formation
and small blood vessel occlusion
Protection during the acute
phase of the disease
Prevention of organ damage
Reduction in exacerbations
Future standard of care based on three pillars
Caplacizumab could become the first approved product for the
treatment of aTTP
22
ALX-0171
Wholly-owned anti-RSV Nanobody
• First-in-class trivalent Nanobody, delivered by inhalation
• Developed for the treatment of respiratory syncytial virus (RSV) infection in infants
• 3 Phase I studies in 106 subjects* successfully completed
• First-in-infant Phase IIa on-going with results expected in H1 2016
• Opportunity in multi-billion dollar market
* Of whom 24 adults with hyper-reactive airways
23
RSV infection in infants
• Leading cause of infant hospitalisation and primary viral cause of infant death
– ~65% of infants are infected in their first year of life
– ~300,000 children* (< 5 years) hospitalised per year in 7 major markets1,2 ; ~500-4,500 deaths per year in the US
– ~2.1 million outpatient visits annually in the USA among children <5 years of age
– increased medical cost in the first year following RSV infection3
– prolonged wheezing and increased risk of asthma development4
• No current treatment options available
– Synagis® used as prophylaxis in high-risk pre-term infants only ($900M sales in 2014)
* Extrapolation based on estimated US prevalence 1 Hall et al, NEJM, 2009; 2 Lee et al, Human Vaccines, 2005; 3 Shi et al, J Med Econ, 2011; 4 Sigurs et al, Thorax, 2010; Backman et al, Acta Pediatr, 2014
High unmet medical need
Evolves to
distressing
symptoms
8-20%
hospitalised
Symptomatic treatment
including inhaled
corticosteroids & bronchodilator
24
• Well tolerated in multiple Phase I clinical studies in adults
• Strong in vitro and in vivo study results
– potent anti-viral effect against recent clinical RSV isolates
– 10,000 fold reduction in viral titres and superiority in vitro compared with palivizumab (Synagis®)1
– daily inhalation of ALX-0171 for 3 consecutive days in neonatal lamb model for infant RSV demonstrated markedly reduced signs and symptoms of illness (“Malaise Score”)2 and viral lesions
ALX-0171
1 Vaccines of the World (Oct 2013) 2 RSV Symposium (Nov 2014) – presentations on http://www.ablynx.com/rd-portfolio/clinical-programmes/alx-0171/
Key milestones achieved
Lung viral lesions
(day 6 post infection)
0
20
40
60
80
100
0 1 2 3 4 5 6
% o
f la
mb
s w
ith
sco
re ≥
1
Control
ALX-0171
RSV
infection
Treatment ALX-0171 or
formulation buffer
Malaise score
Mean
% l
un
g t
issu
e w
ith
vir
al le
sio
ns
0
10
20
30
40
50
60
Control ALX-0171
25
ALX-0171
• Infants aged 3 to <24 months who are hospitalised for RSV infection
• Study centres in Europe and Asia-Pacific region
• Custom-developed infant inhalation device (vibrating mesh)
* Data Monitoring Committee
First-in-infant inhalation study on-going
RA
ND
OM
ISA
TIO
N
2:1
Placebo N=10 Inhaled ALX-0171 once/day
3 consecutive days
ALX-0171 N=20
Open-label lead-in
N=5 Review
by DMC*
Inhaled ALX-0171 once/day or
placebo
3 consecutive days
Primary endpoint:
Safety and tolerability of ALX-0171
Secondary endpoints:
Clinical effect (feeding, respiratory rate,
wheezing, coughing, general appearance)
PD (viral load), PK (ALX-0171 systemic
concentration) and immunogenicity
Results expected H1 2016
26
ALX-0061
Anti-IL-6R Nanobody partnered with AbbVie
• Half-life extended Nanobody
• Best-in-class potential for the treatment of
auto-immune disorders
• Global licensing agreement with AbbVie
• 2 Phase IIb studies in RA with results
expected H2 2016; Phase II study in SLE
with results expected in 2018
• Opportunity in multi-billion dollar markets
RA: rheumatoid arthritis
SLE: systemic lupus erythematosus
27
ALX-0061
Compelling Phase IIa results in RA patients
83
71
58 63
29
0
20
40
60
80
100
% o
f p
ati
en
ts
All unmodified ALX-0061 at week 24 (N=24)
ACR20 ACR50 ACR70 DAS28 remission Boolean remission
ACR50 score as potential
differentiating factor
Data published 13 February 2013: press release available on Ablynx ‘s website
28
ALX-0061
• $175M upfront at signing in September 2013
• $665M total potential milestones plus double-digit royalties
Global licensing deal with AbbVie
28
Economics
Ablynx • Perform and fund Phase I study with subcutaneous formulation
(successfully completed in 2014)
• Perform and fund Phase II studies in RA and SLE (on-going)
AbbVie
Commercialisation
• Pay a fee for each indication if they exercise the right to
license ALX-0061 after completion of the Phase II studies
• Responsible for Phase III development and registration
• AbbVie is responsible for global commercialisation
• Ablynx retains option to co-promote ALX-0061 in the Benelux
29
ALX-0061
Key data points in clinical development
Phase I
sc study
Phase IIb
combination and
monotherapy
studies in RA
Phase II study
in SLE
2014 2015 2016 2017 2018 2019
Top line results
Top line results
potentially continues development in RA
potentially continues
development in SLE
Results announced 23 Oct 2014
ALX-0061 showed >80% bioavailability after sc injection
Phase II RA OLE
study
Outlook
31
Long term value creation
Potential clinical and regulatory key events
2
2016
2017
2018
ALX-0171 Infant Phase IIa (RSV)
Wholly-owned
ALX-0061 Phase IIb combination therapy (RA)
AbbVie have option to license worldwide
ALX-0061 Phase IIb monotherapy (RA)
AbbVie have option to license worldwide
Caplacizumab MAA filing EU + Phase III results (TTP)
Wholly-owned
ALX-0171 Infant Phase IIb (RSV)
Wholly-owned
ALX-0141 and ozoralizumab Phase I/II in China
Licensed to Eddingpharm (China)
ALX-0761 Phase IIa (psoriasis)
Licensed to Merck KGaA (worldwide)
Caplacizumab conditional approval EU and BLA filing in US
Wholly-owned
ALX-0061 Phase II (SLE)
AbbVie have option to license worldwide
Results from various patient studies with partners
Clinical study results
Key regulatory events
ALX-0761 Phase Ib POC (psoriasis)
Licensed to Merck KGaA (worldwide)
CONTACT DETAILS
Questions
+32 9 262 00 00 Investor
Relations
investors@
ablynx.com www.ablynx.com